Traumatic brain injury (TBI) is a significant health care problem affecting over two million people a year. Although the pathobiology of all forms of TBI has not been completed characterized, most information suggests that, in the case of mild, moderate and severe TBI, axons are preferentially vulnerable to the forces of injury and that their injury explains much of the morbidity initially seen after TBI. with injury, axons are diffusely damaged throughout the brain with the result that damaged axons approximate undamaged axons of the same type. It is our premise that this situation allows the related undamaged fibers to sprout and reoccupy those synaptic sites deafferentated by the diffuse axonal injury, thereby contributing to the recovery seen with mild and some moderate injuries. This premise will be explored in well- controlled animal models of TBI known to produce diffuse axonal injury in specific brain sites. Anesthetized cats and rats will be subjected to moderate TBI and followed over an extended posttraumatic course. In the early postinjury period, antibodies to the 68kD neurofilament subunit will be employed to detect specific nuclear regions demonstrating axonal damage and therein the temporal course and pattern of perisomatic terminal loss a recovery will be followed. This will be accomplished by immunocytochemical approaches conducted at both the LM and EM level. These same approaches will be repeated in animals subjected to severe TBI to determine if the observed terminal loss and recovery replicates that seen with moderate TBI. The damaging consequences of a secondary sublethal ischemic insult on any recovery seen with moderate TBI will be assessed to gain further insight into the causes of less than optimal recovery seen in some moderate and virtually all severe TBIs. In concert with the above studies, the axonal events first associated with the genesis of TBI-induced change as well as those axonal changes occurring late in the postinjury course will be assessed through the use of antibodies to the 68kD subunit and anterogradely transported PHA-L respectively.